Microbioreactors to manipulate oxygen tension and shear stress in the microenvironment of vascular stem and progenitor cells

Abaci, Hasan Erbil; Devendra, R.; Soman, Rohan; Drazer, Germán; Gerecht, Sharon

doi:10.1002/bab.1010

Cited by 28 publications

(33 citation statements)

References 34 publications

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“…Using the capabilities of the microfluidic system previously developed in our laboratory16, we mimicked healthy conditions where cultured cells can be maintained at physiological shear stress and O 2 tension (i.e. 12 dyn/cm 2 and 5% O 2 (38 mmHg)) as well as ischemic conditions (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…The time points were initially chosen based on previous studies focused on the formation of continuous adherent junctions2324. In addition, DO levels in the cell culture media were continuously monitored using O 2 sensor patches at the inlet and outlet of the microchannel111625 throughout the experiments at each condition (Figure 1B). …”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, only a small number of studies thoroughly demonstrated the establishment of an in vivo mimicking EC phenotype in physiological/pathological states1415. In the first part of the study, we establish a microfluidic vascular model (μVM) recapitulating both physiological shear stress and O 2 levels in a device that was recently developed in our lab16. We begin by demonstrating time-dependent transition of human ECs from in vitro phenotype to physiologically relevant phenotypes.…”

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confidence: 99%

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Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

Abaci

Shen

Tan

et al. 2014

Sci Rep

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Studying human vascular disease in conventional cell cultures and in animal models does not effectively mimic the complex vascular microenvironment and may not accurately predict vascular responses in humans. We utilized a microfluidic device to recapitulate both shear stress and O2 levels in health and disease, establishing a microfluidic vascular model (μVM). Maintaining human endothelial cells (ECs) in healthy-mimicking conditions resulted in conversion to a physiological phenotype namely cell elongation, reduced proliferation, lowered angiogenic gene expression and formation of actin cortical rim and continuous barrier. We next examined the responses of the healthy μVM to a vasotoxic cancer drug, 5-Fluorouracil (5-FU), in comparison with an in vivo mouse model. We found that 5-FU does not induce apoptosis rather vascular hyperpermeability, which can be alleviated by Resveratrol treatment. This effect was confirmed by in vivo findings identifying a vasoprotecting strategy by the adjunct therapy of 5-FU with Resveratrol. The μVM of ischemic disease demonstrated the transition of ECs from a quiescent to an activated state, with higher proliferation rate, upregulation of angiogenic genes, and impaired barrier integrity. The μVM offers opportunities to study and predict human ECs with physiologically relevant phenotypes in healthy, pathological and drug-treated environments.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

Abaci

Shen

Tan

et al. 2014

Sci Rep

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“…3f). For real-time monitoring of pO 2 in the medium, a non-invasive O 2 sensor and optical fiber probe were equipped to the bioreactor (Abaci et al, 2012). We show that the pO 2 was kept above 15% (Fig.…”

Section: Resultsmentioning

confidence: 99%

Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions

et al. 2013

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Large-scale production of human induced pluripotent stem cells (hiPSCs) by robust and economic methods has been one of the major challenges for translational realization of hiPSC technology. Here we demonstrate a scalable culture system for hiPSC expansion using the E8 chemically defined and xeno-free medium under either adherent or suspension conditions. To optimize suspension conditions guided by a computational simulation, we developed a method to efficiently expand hiPSCs as undifferentiated aggregates in spinner flasks. Serial passaging of two different hiPSC lines in the spinner flasks using the E8 medium preserved their normal karyotype and expression of undifferentiated state markers of TRA-1–60, SSEA4, OCT4, and NANOG. The hiPSCs cultured in spinner flasks for more than 10 passages not only could be remained pluripotent as indicated by in vitro and in vivo assays, but also could be efficiently induced toward mesodermal and hematopoietic differentiation. Furthermore, we established a xeno-free protocol of single-cell cryopreservation and recovery for the scalable production of hiPSCs in spinner flasks. This system is the first to enable an efficient scale-up bioprocess in completely xeno-free condition for the expansion and cryopreservation of hiPSCs with the quantity and quality compliant for clinical applications.

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“…Temperature was shown to significantly affect the early development of the embryo. Other factors include dissolved oxygen, compressive pressure and electricity also proved to have influence on stem cell differentiation [120][121][122].…”

Section: Stem Cell Biologymentioning

confidence: 99%

Development and Applications of Microfluidic Devices for Cell Culture in Cell Biology

Yi¹,

Lin²

2016

Mol Biol

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Development of microfluidic culture technology combined with tissue engineering catalyzes the progress in study of cell biology. These tools will promote the understanding of physiological and pathological changes. Cancer cells and stem cells are sensitive to their surroundings, thus could be better explored by controllable microfluidic devices. In this review, we describe the ways to control cell microenvironment and explain how the influencing factors influence cellular behaviors, then present microfluidic-chip-based exemplary applications for cancer models and stem cell differentiation.

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Microbioreactors to manipulate oxygen tension and shear stress in the microenvironment of vascular stem and progenitor cells

Cited by 28 publications

References 34 publications

Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

Scalable expansion of human induced pluripotent stem cells in the defined xeno-free E8 medium under adherent and suspension culture conditions

Development and Applications of Microfluidic Devices for Cell Culture in Cell Biology

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